SLE is a relatively common disease of young women. The disease carries a significant morbidity and mortality. Few, if any, significant therapeutic advances have been made since the introduction of corticosteroids. In this SCOR application, basic scientists and clinical investigators have combined their expertise and resources at the three Cornell affiliated Hospitals in New York City to address fundamental defects in SLE. These collaborative interactions will involve 10 laboratories and will utilize already existing Core Facilities. This research base combined with a very large SLE population at HSS, a computerized clinical database and high quality of clinical care, provide the essential environment for this SCOR application. The underlying theme of all of these projects is defects / polymorphisms which are responsible for the abnormalities leading to expression of SLE. In one case this involves defects in molecules controlling tolerance (project 1), in the second (project 2), molecules controlling T-B lymphocyte interaction and, in project 3, molecules that either induce thrombosis or predispose certain patients to develop thrombotic complications. The long term goal of this program is to apply the basic knowledge obtained in these studies to develop new therapeutic approaches to treating SLE. To this end, a Therapeutics Core has been created which will encourage and facilitate new treatment strategies.